Biomaterials Res. Center, KIST

Bioengineering on arterial system

2006. 3. 4

생체재료 연구센터

김 수 현

Biomaterials Res. Center, KIST

Cell-sheet Engineering

Beating cardiac patch

Biomaterials Res. Center, KIST

Regenerative cornea

cell sheet

Biomaterials Res. Center, KIST

Biomaterials Res. Center, KIST

대구경 ( >6mm)

인공혈관 : Dacron, ePTFE 시판, 상용화/반영구적

성장기 환자에 적용불가

연구개발 목적-심혈관

소구경(

Biomaterials Res. Center, KIST

Key Elements in Tissue Engineering

Cells

Scaffold

Tissue

Signal

Materials,Structure,

Porosity, Function

Mechanically active cellsAutologous cells

Stem cell technology

Growth factorsAdhesion moleculesMechanical signals

Differentiation factor

Biomaterials Res. Center, KIST

Elasticity of polymers

Mechanical stimuli

Tissue engineered bio-organ regeneration having good

performance

In-vitro/vivo experiments for tissue

engineering

High elasticityBiodegradabilityHigh cell affinity

Mechano-active biomaterials

Mechanical stimuliHigh kinetic rate

High mass transfer

Mechano-active bioreactors

Mechano-active Tissue engineering

Strategy

Biomaterials Res. Center, KIST

Elastic and flexible behaviors of PLCL scaffold

Stretching RecoveryOriginal

Twistable FoldablePLGA (7:3)Broken at 20% strain

Biomaterials Res. Center, KIST

PLCL in CHCl3

Salt (NaCl),

Various sizes of 50-200 um

Various porosity of 60-95 %

Fabrication of tubular PLCL scaffolds

ID = 4 mm,

t = 1 mm

Biomaterials Res. Center, KIST

SMC & EC

Culture (3)

SMC & EC isolation

Rabbit artery

Subculture

SMCs seeded on PLCLcoated w. collagen

Static culture

No mechanical stimulation

(Medium: M199, 2 passage)

( 2.0 x 106 cells)

Smooth muscle cell Endothelial cell

In vitro SMCs static cultured stabilized for 1-7 days

In vitro ECs culture on a bioreactor, 1 w

SMCs culture on a bioreactor, 5-8 wMechanical stimulation

Biomaterials Res. Center, KIST

In vitro Cells culture in a bioreactor ; 8 weeks

Cells seeded on

the scaffold

Bioreactor (Pulsatile flow for 8w)

Regenerated vascular tissue

Biomaterials Res. Center, KIST

ECM analysis

1 2 3 4 5

0.10

0.15

0.20

0.25

0.30

0.35

0.40

Ab

so

rb

an

ce

(5

40

nm

)

weeks

Static condition

Pulsatile condition

1 2 3 4 50.10

0.15

0.20

0.25

0.30

0.35

0.40

0.45

0.50

0.55

Ab

so

rb

an

ce

(4

05

nm

)

weeks

Static condition

Pulsatile condition

Collagen contents Elastin contents

Biomaterials Res. Center, KIST

M-T staining of collagen network in regenerated vessels

Biomaterials Res. Center, KIST

Van-Giesen staining of elastin network in regenerated vessels

Biomaterials Res. Center, KIST

[Smooth Muscle -Actin]

1 3 5 8w 1 3 5

8w43 kDa

[Smooth Muscle Myosin Heavy Chain]

1 3 5 8w 1 3 5

8w204 kDa

Western blotting

static dynamicdynamic static

Biomaterials Res. Center, KIST

Morphology of fibrous scaffolds

5% 7.5% 10%

A B C

D E F

G H I

Controllable diameter size

A-C: surface morphology, D-E: magnification of A-C

G-I: cross-sectional morphology

Fibrous PLCL scaffolds are open-pore structures and well-interconnected

between pores.

Individual fibers are found either fused or forked together with neighboring

fibers

SEM images of fibrous scaffolds

Biomaterials Res. Center, KIST

In vivo

Dog

Dog

Bone marrow

mononuclear cell

Press seeding

Bone marrow

http://images.google.co.kr/imgres?imgurl=http://www.arts.monash.edu.au/korean/klec/Clipart02/KLEC2003_C117.gif&imgrefurl=http://www.arts.monash.edu.au/korean/klec/Clipart/index.php%3FRollID%3DClipart02%26FrameID%3DKLEC2003_C117&h=266&w=400&sz=7&tbnid=n6O6JyzmqIei5M:&tbnh=79&tbnw=120&hl=ko&start=6&prev=/images%3Fq%3D%25EA%25B0%259C%26svnum%3D10%26hl%3Dko%26lr%3D%26newwindow%3D1%26sa%3DGhttp://images.google.co.kr/imgres?imgurl=http://www.arts.monash.edu.au/korean/klec/Clipart02/KLEC2003_C117.gif&imgrefurl=http://www.arts.monash.edu.au/korean/klec/Clipart/index.php%3FRollID%3DClipart02%26FrameID%3DKLEC2003_C117&h=266&w=400&sz=7&tbnid=n6O6JyzmqIei5M:&tbnh=79&tbnw=120&hl=ko&start=6&prev=/images%3Fq%3D%25EA%25B0%259C%26svnum%3D10%26hl%3Dko%26lr%3D%26newwindow%3D1%26sa%3DG

Biomaterials Res. Center, KIST

▶ patch type : IVC 8 wks

Inner Outer

Implantation Harvest

Biomaterials Res. Center, KIST

▶ Tube type : abdominal aorta, 4 wks

Scaffold Seeding

Implantation Harvest

Biomaterials Res. Center, KIST

J. of Polymer Sci., Polymer Chem., 39, 7, 973 ( 2001)

J. Biomaterials Sci., Polymer Ed, 12, 10, 1147 (2001)

J. of Polymer Sci., Polymer Chem., 40, 544 (2002)

J. Polymer Sci., Polymer Chem., 40, 15, 2545 (2002)

Macromolecules, 36, 5585 (2003)

J. Biomed. Mat. Res.,66A, 1, 29 (2003).

Biomaterials, 24, 5049 (2003)

Biomaterials, 25, 2979 (2004)

J. of Biomat. Sci., Polymer ed., 15, 5, 645 (2004)

Biomaterials, 25, 5939 (2004)

Macromolecular Bioscience, 4, 802 (2004)

Biomacromolecules, 5, 1303 (2004)

Biomaterials, 26, 1405 (2005)

Biomaterials, 26, 1915 (2005)

Cover Page : J. Biomed. Mat. Res., July (2003)

Tissue Engineering : Mechano-active Tissue Engineering